c Task 3: Fluorescence tomography attachment for photoacoustic imaging (Joseph Culver) 8.C.1 Specific aims: This task specific project will combine fluorescence diffuse optical tomography (DOT) instrumentation with PAT imaging to provide a system for imaging breast tissue with concurrent molecular-, functional-, and anatomical- contrasts. While PAT provides high resolution images of absorption contrast, fluorescence contrasts provide unique reporting mechanisms that can be engineered for exquisite sensitivity to local biological environments. The power of fluorescence contrast is evident in the ubiquitous use of fluorescence in studies of molecular cell biology and in the rapid recent growth of fluorescence for in vivo imaging. Combining DOT with PAT adds the power of fluorescence to the high resolution capabilities of PAT. Furthermore DOT and PAT are complementary in that DOT has high sensitivity to volume averaged contrasts in capillary beds while PAT has high sensitivity to contrast in arteries, arterioles and venules and veins. We have previously developed a camera based fluorescence tomography system for small animals and a discrete-detector based DOT system for high speed (10 Hz) neuroimaging of adult humans at depths up to 2-3 cm. To incorporate DOT into PAT we will develop a DOT fiber array system that attaches to the periphery of the PAT device for concurrent co-registered imaging. Aim 1: Develop a fiber ring fluorescence tomography system - Building on our existing high-dynamic range DOT platform (Zeff et al. PNAS 2007 ref. [168]), we will develop a real-time fiber based fluorescence DOT instrument that is compatible with PAT. We will establish sensitivity, dynamic range for imaging in both absorption and fluorescence detection modes. The feasibility of imaging within the context of current human lymph node procedures will be established by imaging methelyene blue (MB). The feasibility imaging fluorophores for molecular targeting will be established by imaging cypate (CY). Aim 2: Integrate fluorescence tomography with PAT- Concurrent DOT-PAT will be developed and established with in vivo imaging. The DOT images of molecular contrast data will be of lower resolution while PAT data provides higher resolution anatomical and functional images. The multimodal images will be combined implicitly through co-registration and explicitly through the DOT reconstruction process.